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Rituximab for very low dose steroid-dependent nephrotic syndrome in children: a randomized controlled study

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Abstract

Background

Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, randomized controlled trial was designed to test whether the monoclonal antibody rituximab is non-inferior to steroids in maintaining remission in juvenile forms of SDNS and how long remission may last (EudraCT:2008-004486-26).

Methods

We enrolled 30 children 4–15 years who had developed SDNS 6–12 months before and were maintained in remission with low prednisone doses (0.1–0.4 mg/Kg/day). Participants were randomized following a non-inferiority design to continue prednisone alone (n 15, controls) or to add a single intravenous infusion of rituximab (375 mg/m2, n 15 intervention). Prednisone was tapered in both arms after 1 month. Children assigned to the control arm were allowed to receive rituximab to treat disease relapse.

Results

Proteinuria increased at 3 months in the prednisone group (from 0.14 to 1.5 g/day) (p < 0.001) and remained unchanged in the rituximab group (0.14 g/day). Fourteen children in the control arm relapsed within 6 months. Thirteen children assigned to rituximab (87%) were still in remission at 1 year and 8 (53%) at 4 years. Responses were similar in children of the control group who received rituximab to treat disease relapse. We did not record significant adverse events.

Conclusions

Rituximab was non-inferior to steroids for the treatment of juvenile SDNS. One in two children remains in remission at 4 years following a single infusion of rituximab, without significant adverse events. Further studies are needed to clarify the superiority of rituximab over low-dose corticosteroid as a treatment of SDNS.

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Funding

This study was supported by Istituto Giannina Gaslini deriving from ‘Cinque per mille of IRPEF-Finanziamento della ricerca sanitaria’, the Italian Ministry of Health, The Renal Child Foundation, and the ‘Fondazione La Nuova Speranza’ (‘Progetto integrato per la definizione dei meccanismi implicati nella glomerulosclerosi focale’). GMG received a grant from Compagnia San Paolo (ROL-9849).

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Author notes

  1. Pietro Ravani, Francesca Lugani and Gian Marco Ghiggeri contributed equally to this work.

Authors and Affiliations

  1. Division of Nephrology, Faculty of Medicine, Foothills Medical Centre, University of Calgary, 1403-29th Street NW, Calgary, AB, T2N 2T9, Canada

    Pietro Ravani

  2. Division of Nephrology, Dialysis, Transplantation, Giannina Gaslini Children’s Hospital, Via Gerolamo Gaslini 5, 16148, Genoa, Italy

    Francesca Lugani, Monica Bodria, Giorgio Piaggio & Gian Marco Ghiggeri

  3. Department of Medicine and Surgery, Division of Nephrology, School of Nephrology, University of Parma, Parma, Italy

    Isabella Pisani & Domenico Bartolomeo

  4. School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland

    Marco Prunotto

Authors
  1. Pietro Ravani
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  2. Francesca Lugani
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  3. Isabella Pisani
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  4. Monica Bodria
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  5. Giorgio Piaggio
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  6. Domenico Bartolomeo
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  7. Marco Prunotto
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  8. Gian Marco Ghiggeri
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Corresponding authors

Correspondence to Pietro Ravani or Gian Marco Ghiggeri.

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Conflict of interest

All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organization for the submitted work; no financial relationships with any organization that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work.

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Ravani, P., Lugani, F., Pisani, I. et al. Rituximab for very low dose steroid-dependent nephrotic syndrome in children: a randomized controlled study. Pediatr Nephrol 35, 1437–1444 (2020). https://doi.org/10.1007/s00467-020-04540-4

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  • DOI: https://doi.org/10.1007/s00467-020-04540-4

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